Synthesis and evaluation of analogues Indole-based agents as Tubulin inhibitors using Cell lines

Abstract

Back ground : Combretastatin is a natural stilbene compound. These molecules generally have three similar features: the trimethoxy ring "A", the ring "B", which usually has substitutions between C3' and C4', and the ethylene bridge between the two rings to give the necessary rigidity to the structure. Members of the combretastatin family have different abilities to act on vascular tumors. Combretastatin binds to the colchicine binding site of the tubulin beta subunit. Despite the similar name, combretastatin is not related to the statin family of cholesterol-lowering drugs.

Results: A novel combretastatin 2-(1-acetyl-1H-indol-3-yl)-3-(phenyl)acrylic acid analog was synthesized from the A ring position of combretastatin (CA4) (2a to 2j). is an indole moiety and has been evaluated for immunogenicity against various cancer cells such as THP-1 (leukemia), A-549 (cancer), IGROV-1 (ovarian), HEP-2 (liver), MCF-7 (breast) and DU. -145 (prostate). Compound 2d has anti-cancer activity against THP-1 and MCF-7 with IC50 of 0.80 and 0.37 μM, respectively.

Summary: Immunofluorescence technology confirmed that the target binding to the colchicine binding site is located at the α and β interface of tubulin, preventing polymerization. Molecular docking further confirmed that the active 2d product binds to the colchicine binding site at the α and β interfaces of tubulin. Hot Tags: colchicine binding site, indolyl combretastatin, molecular docking, tubulin inhibitor.